High-Altitude Flight May Harm Pilot's Brain

Action Points

This study of U-2 pilots demonstrated a marked increase in the number and volume of white matter hyperintensities on brain MRI as compared with healthy controls.

While interesting, this finding is of limited clinical utility without a deeper understanding of the pathogenic mechanism at work at high altitudes.

Military pilots exposed to high-altitude hypobaria had significant changes in the number, volume, and distribution of white-matter hyperintensities in the brain, consistent with effects of microemboli, an imaging-based study showed.

As compared with healthy controls, the pilots' brains had a 375% greater volume of white-matter hyperintensity on MRI and nearly a 300% increase in the number of areas of white-matter hyperintensity, according to Stephen McGuire, MD, of the University of Texas Health Science Center at San Antonio.

White-matter hyperintensities were uniformly distributed throughout the pilots' brains, whereas hyperintensities exhibited predominately frontal distribution in the control group, they reported online in Neurology.

"This is consistent with our hypothesized pattern of damage produced by interaction between microemboli and cerebral tissue, leading to thrombosis, coagulation, inflammation, and/or activation of innate immune response, although further studies will be necessary to clarify the pathologic mechanisms responsible," the authors concluded.

The findings build off those of a prior study by the same group showing that neurologic decompression sickness is associated with increased white-matter hyperintensities among pilots of high-altitude U-2 reconnaissance aircraft. Investigators sought to quantify the volume, number, and regional distribution of white-matter hyperintensities in pilots and a matched control group of healthy individuals.

McGuire and colleagues hypothesized that increased white-matter hyperintensities in pilots were associated with hypobaria-derived microbubbles. They further hypothesized that the U-2 pilot population would have significantly greater subcortical white-matter hyperintensity volume and number and a more uniform distribution as compared with MRI results of the control group.

The study involved 105 active-duty pilots of U-2 aircraft and a control group of 82. All of the study participants underwent three-dimensional, T2-weighted, high-resolution MRI. Investigators compared whole-brain and regional white-matter hyperintensities volume in the pilots and control group.

The pilots had a mean white-matter hyperintensity volume of 0.134 cm3, which increased to 0.155 cm3 after site-specific adjustment. That compared with a mean of 0.042 cm3 in the control group, representing a 375% increase in the pilots (P=0.004). White-matter hyperintensities count averaged 3.29 in the control group and 7.57 (9.67 adjusted) in the pilots, a 294% difference (P<0.001).

Frontal-lobe lesions accounted for the largest fraction of white-matter hyperintensity volume and number in pilots (50% and 56% respectively) and the control group (69% and 70%). As compared with the control group, pilots had significantly higher white-matter hyperintensities volume in the frontal, insula, limbic, sublobar, and temporal regions (P<0.01). Pilots also had significantly more white-matter hyperintensities in the insula, limbic, temporal, and sublobar regions (P<0.01).

Analysis of regional heterogeneity showed that white-matter hyperintensities volume deviated in two regions among pilots (insula and temporal lobe) as compared with five in the control group. Analysis of regional heterogeneity for lesion number showed more uniform distribution in pilots versus participants in the control group.

The volume and number of white-matter hyperintensities are markers of cerebral integrity, the authors noted. Higher volume and number of white-matter hyperintensities correlate with age-related cognitive decline.

Heterogeneity in the distribution of white-matter hyperintensities occurs in normal aging, they continued. Most lesions (60% to 80%) occur in the frontal area. A more uniform distribution of white-matter hyperintensities are characteristics of neuroinflammatory disorders and traumatic brain injury.

"This study demonstrated that pilots exposed to hypobaria had increased volume and number of subcortical white-matter hyperintensities compared with a healthy, age- and education-matched normative population," the authors said. "White-matter hyperintensities in pilots were more uniformly distributed throughout the brain than in normal controls and did not increase with age in pilots, suggesting that hypobaric exposure produces white-matter damage different from that occurring in normal aging."

The findings are both intriguing and consistent with reports in high-altitude climbers, according to Gary Strangman, PhD, of Harvard and Massachusetts General Hospital.

"The fact that elevated white-matter hyperintensities were observed in the absence of hypoxia provides additional evidence suggesting a unique contribution of hypobaria to cerebral injury," said Strangman, who is conducting studies of brain changes with and without hypoxia and hyperbaria in collaboration with the United States Army Research Institute of Environmental Medicine.

"The mechanism underlying hypobaric effects on cerebral integrity remain to be understood, but given their novelty they warrant further investigation."

The study was supported by the United States Air Force Surgeon General grants.

McGuire reported no conflicts of interest. One or more co-authors disclosed relationships with US WorldMeds, Schizophrenia Bulletin, and Wiley-Blackwell.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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